Publication Type
Journal Article
Version
publishedVersion
Publication Date
9-2024
Abstract
Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.
Discipline
Econometrics | Health Economics | Medical Sciences
Research Areas
Econometrics
Publication
The Journal of Clinical Investigation
Volume
134
Issue
17
First Page
1
Last Page
17
ISSN
0021-9738
Identifier
10.1172/JCI178711
Publisher
American Society for Clinical Investigation
Citation
Sati, S.; Huang, J.; Kersh, A.E.; Jones, P.; Ahart, O.; Murphy, C.; Prouty, S.M.; Hedberg, M.L.; Jain, V.; Gregory, S.G.; LEUNG, Denis H. Y.; Seykora, J.T.; Rosenbach, M.; and Leung, T.H..
Recruitment of CXCR4+type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases. (2024). The Journal of Clinical Investigation. 134, (17), 1-17.
Available at: https://ink.library.smu.edu.sg/soe_research/2822
Copyright Owner and License
Author-CC-BY
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Additional URL
https://doi.org/10.1172/JCI178711